2010 — 2020 |
Bruno, Randy M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Role of Dendrites in Thalamocortical Circuitry @ Columbia University Health Sciences
? DESCRIPTION (provided by applicant): Dysfunctions of the cerebral cortex, the highest-level processor of our sensations, perceptions, and decisions, are thought to underlie numerous neurological and psychiatric disorders. A major obstacle to treating such pathology is the high degree of complexity of cortical circuitry, which has remained largely enigmatic. Each primary sensory area of cortex receives connections from a primary and secondary thalamic nucleus. Strokes destroying primary thalamic nuclei cause near complete loss of sensation, but damage to secondary thalamus produces complex behavioral deficits. Secondary thalamus is also connected with diverse cortical areas, suggesting a possible role in psychiatric disorders. Nevertheless, the functions of secondary thalamus remain unknown. Are secondary nuclei alternate sensory pathways to cortex? Or key sources of behavioral signals? This project will focus on the secondary somatosensory thalamus (the posterior medial nucleus, POm). POm has sometimes been regarded as an afferent sensory pathway, operating in parallel with the primary thalamic relay, but several studies support the view that POm is instead downstream of primary somatosensory cortex. POm has been suspected of mediating communication between cortical areas and, more recently, to aggregate motor signals to provide as feedback to cortical areas. Like secondary visual thalamus, POm may also have a role in selectively enhancing particular stimuli. The first goal of this project is to investigate coding of sensory, motor and behavioral signals in POm. The second goal is to understand their functional impact on primary somatosensory cortex, particularly on apical dendrites in cortical layer 1-a major target of POm. The third goal is to determine whether or not simple sensory behaviors require POm. To achieve these goals, we will combine mouse behavior with electrophysiology, two-photon microscopy, and optogenetics. We aim to identify the role of this long obscure circuit component in somatosensation. Identifying fundamental functions of this secondary thalamic nucleus will likely pave the way for future studies in other neocortical systems and in higher-order species.
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2016 — 2020 |
Bruno, Randy M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Behavioral Functions of Upper and Lower Cortical Layers @ Columbia University Health Sciences
PROJECT SUMMARY/ABSTRACT The cerebral cortex mediates all of human and animal cognition, encompassing a diverse set of abilities including sensation, perception, decision making, and motor planning. Dysfunctions of the cerebral cortex are thought to underlie numerous neurological and psychiatric disorders. A major obstacle both to understanding normal behaving and to treating pathology is the high degree of complexity of cortical circuitry, which has remained largely enigmatic. The conventional view of neocortex has been that sensory processing begins in layer 4 (L4), which was identified a century ago as the principal target of thalamic axons carrying information from our sensory organs. Sensory transforms are widely believed to occur as excitation spreads serially along the densest axonal pathways (thalamus?L4?L2/3?L5/6). Recently we discovered that the cerebral cortex, rather than being a monolithic structure, may contain two entirely separate processing systems, activated by the same signals arising from the thalamus. L4 is thus not an obligatory distribution hub for cortical activity, and thalamus activates two distinct ?strata? of cortex in parallel. This proposal's goal is to identify the behavioral and computational roles of the upper (L2-4) and lower strata (L5/6) as well as the interactions between them. We will investigate the behavioral roles of these layers in the mouse whisker system. Specific layers will be optogenetically disrupted in a series of tactile behavioral tasks, in which task complexity is progressively increased. Interlaminar interactions will also be studied by recording electrophysiologically from specific layers during behavior and using novel machine learning techniques designed to identify the type of computation performed in different levels of ?deep networks?. The dimensionality of the representation in a layer will be estimated under normal behaviors and when specific layers are inactivated. Identifying fundamental functions of upper versus cortical layers will likely pave the way for future studies in other neocortical systems and in higher-order species. Moreover, as the different layers contain molecularly and biophysically distinct cell types and project to distinct downstream targets, specific neurological disorders may involve dysfunction of specific pathways, cell types, and layers. Establishing the behavioral and computational roles of these elements may contribute to development of targeted therapies.
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